This invention relates to a structure for performing measurement through use of a thin film device.
A nanopore sequencer is a system configured to measure a current value of an object to be measured that passes through a nanopore embedded in a thin film. For example, when the object to be measured is deoxyribonucleic acid (DNA), and the DNA passes through the nanopore, a current value for sealing the nanopore (hereinafter referred to as “sealing current value”) varies depending on a difference in base (adenine (A), guanine (G), cytosine (C), or thymine (T)) forming the DNA. With this, the nanopore sequencer can identify a base sequence.
As factors for determining DNA reading accuracy of the nanopore sequencer, there are given, for example, the thickness of a thin film in which a nanopore is formed, and the magnitude of noise of a current that passes through the nanopore. It is preferred that the thickness of the thin film be small. Each interval between adjacent bases of four kinds of bases arranged in a DNA strand is about 0.34 nanometer. As the thickness of the thin film becomes larger as compared to the interval, a larger number of bases simultaneously enter the nanopore, and hence a signal obtained as a sealing current is a signal derived from a plurality of bases. Therefore, the determination accuracy of a base sequence is deteriorated, and signal analysis also becomes more complicated. It is also preferred that a noise current be smaller. The noise current is added to a value of the sealing current. In order to increase an identification rate of the four kinds of bases, it is required that the sealing current be reduced.
In a document of Venta (Venta, K., et al., Differentiation of Short, Single-Stranded DNA Homopolymers in Solid-State Nanopores, ACS Nano 7(5), pp. 4629-4636 (2013)), it is disclosed that a difference in sealing current derived from base kinds at a time when the DNA passes through the nanopore of the thin film is observed. In this document of Venta, in order to increase an identification rate of the sealing current, a nanopore is formed in a SiN membrane of a thin film, and an insulating film is applied thereto. With this, a device capacitance is decreased to reduce a noise current.
A thin film for biological polymer measurement has a problem in that the thin film is liable to be influenced by a potential difference between solutions on both sides of the thin film and breaks due to the potential difference. In particular, when the device capacitance is decreased in order to reduce the noise current, the probability that an initial defect occurs in the thin film increases.
It was verified by an experiment that the noise current was able to be reduced by applying an insulating film to a device including a thin film membrane having a thickness of from 12 nanometers to 20 nanometers to decrease the device capacitance. Meanwhile, it was verified that, when solutions were filled in chambers on both surface sides of the thin film of a low-capacitance device having reduced noise, an initial defect in which the thin film broke occurred in most cases. This initial defect is not referred to in the document of Venta. Therefore, the mechanism of the initial defect and the countermeasures against the initial defect remain unknown.
As a result of the investigation, it was found that the initial defect occurred when a potential difference ΔV(=ΔQ/C) applied to the thin film increased along with decrease in device capacitance C depending on a charge difference ΔQ of the solutions filled on both sides of the thin film, to thereby subject the thin film to dielectric breakdown. Further, it was found that one of major factors of the occurrence of the charge difference was static electricity generated on an outer side of a solution tank in which the solution was filled.
The static electricity is generated when substances approach each other up to about several nanometers or less and are charged by contact friction. It has been known that, when two kinds of substances are charged by contact friction, the charge amount thereof varies depending on the substance. In a method using a substance formed of the same material as that for a substance to be subjected to contact friction or a substance close to the substance to be subjected to contact friction in triboelectric series, a partner substance to be subjected to contact friction is limited. Thus, there is a risk in that the substance is charged through a change in atmospheric condition or contact friction with another substance. Further, countermeasures for adjusting the atmospheric condition, such as accelerating discharge by raising humidity or using an ionizer, require maintenance of equipment for adjusting the atmospheric condition. Further, there is a problem of noise caused by vibration of the equipment for adjusting the atmospheric condition.